A protective role of HTLV-1 gp46-specific neutralizing and antibody-dependent cellular cytotoxicity-inducing antibodies in progression to adult T-cell leukemia (ATL)
| Autor: | Tanaka, Yuetsu, Tanaka, Reiko, Imaizumi, Naoki, Mizuguchi, Mariko, Takahashi, Yoshiaki, Hayashi, Masaki, Miyagi, Takashi, Uchihara, Junnosuke, Ohshiro, Kazuiku, Masuzaki, Hiroaki, Fukushima, Takuya |
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| Rok vydání: | 2022 |
| Předmět: |
Adult
Human T-lymphotropic virus 1 Immunology Antibody-Dependent Cell Cytotoxicity Antibodies Monoclonal neutralization Antibodies Viral Antibodies Neutralizing HTLV-I Infections ATL HTLV-1 antibody Immunoglobulin G gp46 Leukocytes Mononuclear Humans Leukemia-Lymphoma Adult T-Cell Immunology and Allergy ADCC |
| Zdroj: | Frontiers in Immunology. 13 |
| ISSN: | 1664-3224 |
| DOI: | 10.3389/fimmu.2022.921606 |
| Popis: | Human T-cell leukemia virus type-1 (HTLV-1) establishes a long-term persistent infection in humans and causes malignant T-cell leukemia, adult T-cell leukemia (ATL). HTLV-1-specific cytotoxic T lymphocytes have been suggested to play a major role in the immunosurveillance of HTLV-1-infected T cells. However, it remains unclear whether HTLV-1-specific functional antibodies are also involved in the host defense. To explore the role of antibodies in the course of HTLV-1 infection, we quantitated HTLV-1-specific neutralizing and antibody-dependent cellular cytotoxicity (ADCC)-inducing antibody levels in plasma from asymptomatic carriers (ACs) and ATL patients. The levels of neutralizing antibodies, as determined by a syncytium inhibition assay, were significantly lower in acute and chronic ATL patients than in ACs. The levels of ADCC-inducing activity were tested using an autologous pair of HTLV-1-producing cells and cultured natural killer (NK) cells, which showed that the ADCC-inducing activity of IgG at a concentration of 100 µg/ml was comparable between ACs and acute ATL patients. The anti-gp46 antibody IgG levels, determined by ELISA, correlated with those of the neutralizing and ADCC-inducing antibodies. In contrast, the proviral loads did not correlate with any of these antibody levels. NK cells and a monoclonal anti-gp46 antibody reduced the number of HTLV-1 Tax-expressing cells in cultured peripheral blood mononuclear cells from patients with aggressive ATL. These results suggest a protective role for HTLV-1 neutralizing and ADCC-inducing antibodies during the course of HTLV-1 infection. |
| Databáze: | OpenAIRE |
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